DSA10 - Benign Leukocytes, Lymph Nodes Disorders and Review of the Spleen and Thymus

Myeloblast

Prominent Nucleoli (round to oval)

Diffuse immature chromatin (no clumping)

Define Stage of Granulopoiesis

True

T/F - Blasts should NOT be seen in peripheral blood

Promyelocyte

Round nucleus

Reddish-blue and fine to slightly condensed chromatin

Large cell

Primary (Azurophilic) granules appear

Define Stage of Granulopoiesis

Myelocyte

Oval/Round nucleus

Reddish-blue and slightly granular chromatin

Secondary granules appear (with primary granules still there) = Eosinophilic, Neutrophilic & Basophilic granules

Moderate bluish pink cytoplasm

Define Stage of Granulopoiesis

Metamyelocyte

Kidney-bean shaped nucleus

Define Stage of Granulopoiesis

Band-Form Neutrophil

Condensed band-shaped nucleus

Define Stage of Granulopoiesis

Neutrophil

Condensed, multilobed nucleus

Define Stage of Granulopoiesis

Absolute Neutrophil Count (ANC)

What is more important for WBC count - Differential Count or Absolute Neutrophil Count (ANC)?

Neutrophilia

Define this WBC Abnormality:

Increase in Neutrophils in peripheral blood

-Hx:

> Infex

> Cancer

> Meds

> Metabolic Disorders

> Myeloid Neoplasms

> Constitutional (rare)

More immature leukocytes (signals infection)

What is the significant of a "left shift" in Differential WBC Count?

Exaggerated leukocytosis usually > 50 x 10⁹/L; Usually includes marked neutrophilia with left shift

Define Leukemoid Reaction

Leukoerythroblastic Reaction

Define WBC Abnormality:

BM microenvironment disrupted by metastatic tumor and/or fibrosis

-Hx: Myelophthisis (BM Disruption)

-Dx:

> Left shift w/ circulating immature granulocytic immune cells

> nRBCs

Toxic Granulation (mostly SECONDARY granules)

What is this reactive change in neutrophils?

Cytoplasmic Vacuoles

What is this reactive change in neutrophils?

Dohle Bodies (small, pale blue-gray structures that are found in the cytoplasm of neutrophils, made up of ribosomes and endoplasmic reticulum)

What is this reactive change in neutrophils?

Hypersegmented Neutrophils; Vitamin B12/Folate Deficiency OR Myelodysplastic Syndrome (MDS)/Iron Deficiency/Certain Meds

What is this Neutrophil Abnormality? What might this be a sign of?

Pelger Huet Anomaly (PHA)

ID this Abnormality:

Nuclear Hypersegmentation of Neutrophils - bilobed or mononuclear

-Hx:

> Familial

>> AUTOSOMAL DOMINANT

>> Defect in scaffolding proteins that control shape of nuclear membrane

>> ALL granulocytic lineage affected

>> Neutrophil function normal

> Acquired

>> Meds = sulfa drugs, mycophenolate, ganciclovir, ibuprofen, valproic acid

>> Infex = HIV, influenza, malaria, TB, COVID-19

>> Myelodysplasia

May-Hegglin Anomaly (MHA)

ID this Abnormality:

AUTOSOMAL DOMINANT disorder d/y MYH9 mutation

-Sx:

> Sensorineural hearing loss

> Presenile cataracts

> Glomerular nephropathy

-Dx:

> Dohle like Bodies = Abnormal aggregates of MHY9 protein in neutrophil cytoplasm

> Thrombocytopenia (bleeding tendency)

Chediak-Higashi Syndrome

ID this Abnormality:

Rare AUTOSOMAL RECESSIVE condition --> a/w abnormally large leukocyte granules from fusion of lysozymes

-Sx:

> Partial Oculocutaneous ALBINISM (Giant melanosomes in ocular and skin tissues result in hypopigmentation)

-Dx:

> Platelets LACK dense granules

> Platelet function abnormal

> Deficiency of Serotonin & ADP-containing granules ==> Impaired Platelet aggregation

Alder Reilly Anomaly (ARA)

ID this Abnormality:

Lysosomal stoarge disease from deficiencies of lysosomal enzymes & other essential proteins

-Dx:

> WBCs = Increased Granulations & Inclusions

> Neutrophils = Extreme Toxic Granulation

> Accumulation of undigested substrates (mucopolysaccharides, glycosphingolipids, glycoproteins) d/t enzyme deficiencies

Neutropenia

ID WBC Abnormality:

-Hx:

> Birth/Infancy (Infex, Maternal factors = Autoimmune or Alloantibody, Constitutional)

> Childhood (Infex - usually TRANSIENT Viral Infex)

> Adults

>> Meds/Toxins/Homeopathic Remedies

>> Immune disorder/Chronic Infex

>> Neoplasms

-Prog: Increased Risk of Bacterial Infex

-Tx: Abx Tx & Prophylactic Vaccination

> Bone Marrow (B-cells and other blood cells)
> Thymus (T-cells)

What are the central/generative lymphoid organs?

> Lymph Nodes
> Spleen
> Mucosal & Cutaneous Lymphoid Tissues

What are the peripheral lymphoid organs?

Lymph Node (Cortex = B cells, Paracortex = T cells)

What is this Peripheral Lymphoid Organ?

Lymphocytosis with Reactive Morphology

ID WBC Abnormality Type:

-Hx:

> Viral Infex (EBV/CMV)

Bone Marrow Plasmacytosis

ID Condition:

Increase in polyclonal (polytypic) plasma cells above normal range in bone marrow often accompanied by increased polyclonal serum immunoglobulin levels

-Hx:

> Infex (HIV, Hep C, EBV)

> Autoimmune Disorders

> Marrow Malignancies

-Dx:

> Peripheral = Rouleaux formation

Lymphocytosis w/ Nonreactive Morphology

ID WBC Abnormality Type:

-Hx:

> Pertussis (Whooping Cough)

> Transient Stress

> Persistent Polyclonal B-cell

Bordetella Pertussis (Whooping Cough)

ID Condition:

D/t infection-related toxin blocking migration of lymphocytes form blood to lymphoid organs

-Dx:

> STRIKING Lymphocytosis (up to 10 x 10⁹/L with nonreactive morphology)

-Tx: Abx

Infectious Mononucleosis

ID Condition:

-Hx:

> Epstein Barr Virus (EBV) - type of Herpesvirus

-Path:

> Seronegative “kissing disease” usually involves direct oral contact

> Infects B-cells (becomes activated and proliferate d/t several viral proteins --> produce IgM Abs against capsid proteins)

-Sx/PE:

> Fever

> Sore Throat

> Generalized Lymphadenitis/Lymphadenopathy (in posterior cervical, axillary, groin regions)

> Enlarged Spleen

-Dx:

> Lymphocytosis of activated, CD8+ T Cells

> Marked paracortical expansion and focal areas of necrosis

>> Paracortical (interfollicular) infiltrate was polymorphous and included small lymphocytes

>> Plasmacytoid lymphocytes

>> Plasma cells

>> Occasional medium-sized cells consistent with immunoblasts

Sinus Histiocytosis

ID Condition:

Distention and Prominence of Lymphatic Sinusoids (d/t marked hypertrophy of lining endothelial cells & macrophage infiltrate)

-Hx:

> LNs draining cancers

> Immune Response to Tumor or Tumor Products

> Response to TATTOO PIGMENTS

Cat Scratch Disease (CSD)

ID Condition:

Self-limited lymphadenitis d/t Bartonella henslae (bacteria)

-Hx:

> CHILDHOOD

-Sx/PE:

> Regional LAD (axilla & neck) - 2 wks post inoculation, lasts 2-4 mo

-Dx:

> Histo = Foci of "stellate-microabscesses" (foci of necrosis bounded by palisaded histiocytes)

Large Granular Lymphocytosis

ID WBC Abnormality Type:

-Hx:

> T-cell large granular

> Chronic NK-cell

> Neoplasia
> Postsplenectomy
> Hypersensitive Reactions
> Medication Reaction

What are other causes of Lymphocytosis?

Presentation w/ enlarged lymph nodes

Define Lymphadenopathy

Acute Lymphadenitis

ID Condition:

Acute inflammation of Lymph Node(s)

-Hx:

> Bacterial Infex

-Sx:

> Rubor

> Calor (heat)

> Tumor

> Pain

-Dx:

> Peripheral

>> Few lymphoid cells in necrotic background

>> Follicular hyperplasia

>> Infiltration of PMN Cells

Reactive Follicular Hyperplasia

ID Abnormality:

-Hx:

> RHEUMATOID ARTHRITIS

-Dx:

> Histo = Follicular Hyperplasia + Polyclonal Plasma Cell Infiltration in interfollicular area

> BCL2 Negative (negative since normal germinal center B cells undergo apoptosis w/o appropriate antigen)

> TB
> Histoplasmosis
> Sarcoidosis

What are often causes of Granulomatous Inflammation?

> Typical B cell Rxn
> Rheumatoid Arthritis
> Toxoplasmosis
> Early HIV Infex

What are the causes of Follicular Chronic Lymphadentis?

> Stimulation of Macrophages
> Lymph Nodes draining cancers (Breast Carcinoma)

What are the causes of Sinus Chronic Lymphadentis?

> T-cell Reaction (Acute Viral Infex = Mono)
> Vaccinations (Smallpox)
> Drug Immune Rxns (Phenytoin)

What are the causes of Paracortical Chronic Lymphadentis?

Hemophagocytic lymphohistiocytosis (HLH)

Define Condition:

-Path: Excessive release of IF-gamma from CD8+ T-cells –-> macrophage activation --> release of toxic levels of additional proinflammatory cytokines, such as TNF and IL-6 --> phagocytosis of blood cells and their precursors

-Hx:

> Inherited = D/t defects in genes (ex: PRF1 encoding perforin) that regulates immune cell function

> Acquired = Infex, Malignancy (peripheral T cell lymphoma)

-Sx/PE:

> Fever

> Splenomegaly

-Dx:

> PANCYTOPENIA

> Peripheral = RBCs, Platelets or WBCs WITHIN CYTOPLASM OF MACROPHAGES

> BM = Phagocytic Histiocytes w/ ingested platelets and red cell precursos

Hypersplenism

Define Condition:

Enlarged spleen leading to removal of cellular blood components

-Hx:

> LIVER CIRRHOSIS

> Infex

>> Brucellosis

>> CMV

>> Echinococcus

>> Histoplasmosis

>> Infex Mono

>> Leishmaniasis

>> Schistosomiasis

>> Syphillis

>> Toxoplasmosis

>> TB

>> Typhoid

> Congestive Splenomegaly

> Gaucher Disease

> Hemangioma

> Leukemia/Lymphoma

> Issues of Red Pulp

-Dx

> Widening of splenic cords (Inc macrophages or connective tissue --> premature destruction of normal blood components)

> Reactive Follicular Hyperplasia of White Pulp (if a/w cytopenias)

> Birth = 10-35 gm

> Until Puberty = 20-50 gm

> Progressive Involution = 5-15 gm (elderly)

How does the Thymus change over time?

1. T-cells start in BM as T-cell precursors
2. T-cell precursors leave BM then enter Thymus to undergo maturation
3. Immature Double Negative --> T cells enter thymus at capsule then to cortex for Double Positive --> Further maturation in medullary portion of Thymus for Single Positive T cells
4. Upon maturation, T cells leave thymus & enter circulation & other tissues

What are the stages of T-cell maturation?

DiGeorge Syndrome

Define Condition:

22q11.2 Deletion Syndrome

-Path: Born w/o thymus --> Deficient in T cells (susceptible to infex)

-Hx: INFANTS

-Sx/PE:

> Congenital Heart Defects

> Hypoparathyroidisms

Thymic Follicular Hyperplasia

Define Condition:

Hyperplastic Reactive Lymphoid Follicles w/n Thymus

-Hx:

> Myasthenia Gravis

> Graves Disease

-Dx: MG

> Thymic abnormalities lead to a breakdown in tolerance that causes an autoimmune-mediated attack on acetylcholine receptor (AChR) in myasthenia gravis + More severe EMG Abns

Thymoma

Define Condition:

Tumor originating from epithelial cells of thymus that may be benign OR malignant (carcinoma)

-Hx:

> Associated Autoimmune Disorder (MG, Pure Red Cell Aplasia)

-Sx/PE: D/t Compression of organs

> SVC Syndrome

> Dysphagia

> Cough

> Chest Pain

-Dx: MG

> Benign, Well-Differentiated & Encapsulated (can be REMOVED)